Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Endothelin-1 (ET-1) is elevated in patients with atrial fibrillation (AF) and heart failure. We investigated effects of ET-1 on human atrial cellular electrophysiological measurements expected to influence the genesis and maintenance of AF. Action potential characteristics and L-type Ca2+ current (ICaL) were recorded by whole cell patch clamp, in atrial isolated myocytes obtained from patients in sinus rhythm. Isoproterenol (ISO) at 0.05 μM prolonged the action potential duration at 50% repolarisation (APD50: 54±10 vs 28±5 ms; P<0.05, n=15 cells, 10 patients), but neither late repolarisation nor cellular effective refractory period (ERP) were affected. ET-1 (10 nM) reversed the effect of ISO on APD50, and had no basal effect (in the absence of ISO) on repolarisation or ERP. During repetitive stimulation, ISO (0.05 μM) produced arrhythmic depolarisations (P<0.05). Each was abolished by ET-1 at 10 nM (P<0.05). ISO (0.05 μM) increased peak ICaL from -5.5±0.4 to -14.6±0.9 pA/pF (P<0.05; n=79 cells, 34 patients). ET-1 (10 nM) reversed this effect by 98±10% (P